ABSTRACT: Each year, 225,000 infants in the United States are exposed prenatally to illicit drugs. Women with substance use disorders, particularly those with opioid dependence, are highly vulnerable to cigarette smoking during the perinatal period. Pregnant opioid dependent patients seeking medication-assisted treatment (MAT) have high rates of smoking, ranging from 88% to 95%. Smoking during pregnancy is an independent risk factor (outside of illicit drug use) for several adverse outcomes including ectopic pregnancy, premature birth, orofacial clefts, and sudden infant death syndrome. Illicit opioid use magnifies these risks; among women who use opioids during pregnancy, there is a 6-fold greater risk for intrauterine growth restriction, third trimester vaginal bleeding, preterm delivery, and a majority also will experience neonatal abstinence syndrome (NAS). Prenatal tobacco use significantly increases the severity and duration of NAS, yet is not commonly treated among opioid dependent pregnant women receiving MAT. On average, the healthcare cost per discharged infant with NAS ranges from $39,400 to $53,400; and 77.6% is paid for by Medicaid. MAT has been shown to decrease the severity of NAS compared to no treatment; yet, most opioid dependent women in MAT still continue to smoke cigarettes throughout pregnancy, clearly suggesting that there is a significant need for a comprehensive, evidence- based tobacco treatment intervention. To date, there is no specific pharmacologic or non-pharmacologic tobacco- treatment standard for opioid dependent pregnant women in MAT. More research is needed to develop and test tailored tobacco treatment interventions for pregnant, opioid dependent women. The purpose of this trial is to test a novel intervention for tobacco cessation, Behavioral and Enhanced Perinatal Intervention for Cessation (B-EPIC), in an established community MAT clinic. B-EPIC is designed to reduce tobacco-associated morbidity (e.g., preterm birth, NAS) and healthcare expenditures in pregnant women who are tobacco users receiving buprenorphine for opioid dependence. This two-group randomized and controlled clinical trial (n =100) will provide critical preliminary data to test larger-scale trials. As nearly all B-EPIC services are billable services via public and private insurers; there is high likelihood for sustainability.